Study of Safety and Efficacy of Multiple VAY736 Doses in Patients With Moderate to Severe Primary Sjogren's Syndrome (pSS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 190
- 试验地点
- 10
- 主要终点
- Least Squares Mean Change From Baseline in ESSDAI Score at Week 24
研究概览
简要总结
The purpose of this study was to determine the dose-response relationship of VAY736 for key efficacy and safety parameters
详细描述
This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial that was divided into 4 study periods.
Period 1: A screening period of 4 weeks to assess patient eligibility. Patients could be re-screened only once, and no study-related re-screening procedure could be performed prior to written re-consent by the patient.
Period 2: A blinded treatment period of 24 weeks. At baseline, eligible patients were randomized to one of three ianalumab dose arms (VAY736 5 mg, 50 mg or 300 mg s.c.) or a placebo arm (placebo s.c.). Blinded study drug was administered every four weeks (q4w) for a 24-week period.
Except for Japan, randomization was stratified by baseline ESSDAI score (<10 or ≥10 based on weighted scores). Separate blocks of randomization numbers were generated for patients in Japan versus the other countries participating to ensure that Japanese patients were equally distributed across all treatment groups in the study.
The primary endpoint was assessed at the end of Period 2 (Week 24). Treatment assignment in Period 2 remained double-blinded until the end of Period 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fulfilled revised American European Consensus Group criteria for pSS
- •Seropositive at screening for anti-Ro/SSA antibodies
- •Screening ESSDAI value >=6 scored from 7 domains: articular, cutaneous, glandular, lymphoadenopathy, constitutional, biologic and hematologic.
排除标准
- •Secondary Sjogren's syndrome
- •Use of other investigational drugs
- •Active viral, bacterial or other infections
- •Positive hepatitis B, hepatitis C, HIV or tuberculosis test results at screening
研究组 & 干预措施
VAY736 dose 1 - 5mg
VAY736 low
干预措施: VAY736 (Biological)
VAY736 dose 2 - 50mg
VAY736 medium
干预措施: VAY736 (Biological)
VAY736 dose 3 - 300 mg
VAY736 high
干预措施: VAY736 (Biological)
Placebo
Placebo control
干预措施: Placebo (Other)
结局指标
主要结局
Least Squares Mean Change From Baseline in ESSDAI Score at Week 24
时间窗: Baseline, Week 24
The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score ranging 0-123. Higher scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status.
次要结局
- Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16(Baseline, Week 4, Week 8, Week 12, Week 16)
- Least Squares Mean Change From Baseline in ESSPRI Score at Week 24(Baseline, Week 24)
- Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16(Baseline, Week 4, Week 8, Week 12, Week 16)
- Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks(Baseline, Week 24)
- Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16(Baseline, Weeks 4, 8, 12 and 16)
- Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks(Baseline, Week 24)
- Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16(Baseline, Weeks 4, 8, 12 and 16)
- Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks(Baseline, 24 weeks)
- Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16(Baseline, Weeks 4, 8, 12 and 16)
- Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24(Weeks 4, 8, 12, 16 and 24)
- Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24(Baseline, 24 weeks)
- Percent Change From Baseline in Whole Blood CD19+ B-cell Counts.(Baseline, Week 24, Week 28)
- Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts(Up to two years from last dose patient received.)
- Peak Serum Concentration of VAY736(baseline to week 24, then week 28)